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Shatarat, Amjad (2011) ATP as a sympathetic neurotransmitter. PhD thesis, University of Nottingham.

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Abstract

ATP has been shown to be a sympathetic neurotransmitter in blood vessels. However, its relative importance has been shown to be influenced by the experimental conditions employed such as alteration of the vascular tone. Thus the main aim was to raise the tone of vascular preparations and to further examine sympathetic neurotransmission in these preparations. Porcine whole mesenteries were perfused with physiological buffer and changes in pressure recorded or different sized mesenteric arteries were isolated and set up for isometric recording.

Responses to electrical field stimulation (EFS) were obtained under basal and raised tone conditions induced by U46619, a thromboxane A2 mimetic. The nature of the neurotransmitters involved in the mediation of the electrically-evoked responses was assessed using an α1-adrenoceptor antagonist, prazosin and/or the P2X receptor desensitizing agent, α,β-methyleneATP, an α2-adrenoceptor RX811059 antagonist, and a neuropeptide Y Y1 receptor antagonist BIBP3226. In separate experiments, responses to nerve stimulation were investigated in rat mesenteric small arteries pressurized to 90 mmHg. The effects of a selective α1-adrenoceptor antagonist, YM-12617, and selective P2X1 receptor antagonist, NF-449, on the electrically-evoked response were determined.

Under basal tone conditions the electrically-evoked contractile responses in porcine whole mesenteric bed and isolated arteries were exclusively mediated by noradrenaline (NA) since they were inhibited by prazosin. However, under conditions of raised tone, the electrically-evoked responses were enhanced and a role for ATP was evident since these responses were sensitive to α,β-methyleneATP. Responses to exogenous NA and α,β-methyleneATP were also enhanced at raised tone indicating a postjunctional mechanism of enhancement. Nifedipine attenuated the enhanced responses to EFS and α,β-methyleneATP suggesting a possible role for L-type calcium channels in the mediation of the enhanced responses. In rat pressurised mesenteric arteries the electrically-evoked vasocontractile responses were sensitive to YM-12617 and NF-449, indicating that NA and ATP were involved in the mediation of these responses. Raising tone with U46619 in these arteries enhanced the electrically-evoked contractile response; under these conditions responses were sensitive to both YM-12617 and NF-449.

The present study supports the observation that ATP becomes a more important sympathetic neurotransmitter under conditions of raised tone in contrast to when tone is absent. In porcine mesenteric vascular preparations NA predominates as the main sympathetic neurotransmitter under conditions of basal tone. However, when tone was raised the responses were enhanced and a role for ATP became evident.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Ralevic, V. Dunn, W.R
Subjects:	W Medicine and related subjects (NLM Classification) > WG Cardiocascular system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Biomedical Sciences
Item ID:	12069
Depositing User:	EP, Services
Date Deposited:	16 Jan 2012 12:48
Last Modified:	17 Dec 2017 02:09
URI:	https://eprints.nottingham.ac.uk/id/eprint/12069

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